04/09/2008 02:33 pm ET Updated Nov 17, 2011

If Prescription Meds Don't Kill You They Might Drive You Crazy

It's bad enough that it can drive you crazy trying to get your prescription medications filled, remembering to take them, and figuring out how to pay for them, but now it looks like sometimes your prescription meds themselves can make you, well... nuts.

Hoffmann La-Roche has specialized for years in making drugs with psychiatric side effects like depression and suicidality, including Accutane (acne), Larium (malaria), and Tamiflu (bird flu). Chantix (smoking cessation - Pfizer) has also led to some pretty trippy experiences amongst users. No wonder when you're taking a drug that affects the frontal lobe of the brain. However, Larium gets the door prize for psychiatric side effects, with over half of people who take it developing psychiatric symptoms.

Now it looks like Merck is going to join the rosters of pharmaceutical companies that make drugs that, if they don't kill you, will at least drive you crazy. The FDA recently reported that it is investigating whether the asthma medication, Singulair (montelukast), is associated with an increased risk of suicide.

Montelukast (Singulair) and zafirlukast (Accolate) are part of a new generation of asthma medications that are leukotriene antagonists. These medications work by inhibiting the cysteinyl leukotriene CysLT-1 receptor, which is involved in the inflammatory response. Side effects include headache, gastritis, runny nose, dizziness, nausea, stomach pain, joint pain, and fever. In rare cases they may be associated with Churg-Strauss syndrome, which involves inflammation of the blood vessels. Over the past year Merck has added psychiatric side effects as possible outcomes with Singulair, including tremor (March 2007), depression (April 2007), suicidality (suicidal thinking and behavior, October 2007), and anxiousness (February 2008).

Although a company spokesman denied a causal association between Singulair and depression or suicide, there is cause for concern. There are leukotriene receptors in the brain, and since this drug binds to this receptor and since depression is mediated through the brain, this suggests a mechanism by which Singulair could cause depression. The leukotriene receptors are involved in regulation of the inflammatory response and a link between neural systems involved in the inflammatory response and mood is well established.

Some of the other issues to address in evaluating whether Singulair could cause depression and suicide include whether or not other drugs in this class have similar effects? The FDA is investigating other asthma drugs that work on the leukotriene system, including Accolate and Zyflo, probably with good reason. Are there other cases reported of psychiatric side effects with Singulair that came on after starting the drug, or stopped after the drug was stopped? You can see a number of people reporting all three of these at

If you are on this drug, should you stop it? I don't recommend doing anything without talking to your doctor first. But as always, in the prescription drug department, let the buyer beware.

J. Douglas Bremner, M.D., is author of Before You Take that Pill: Why the Drug Industry May be Bad for Your Health.